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Biomedical subjects

S Fleming

Publications and source records attributed to S Fleming.

At least 55 records · Page 3Linked to original sources
PubMed1998

The effect of aging on bone mineral metabolism and bone mass in Native American women.

OBJECTIVE: To examine the effect of age on mineral metabolism and bone mineral density (BMD) of the hip and spine in Native American women. DESIGN: A cross-sectional study. SETTING: The Sac and Fox Nation in rural Oklahoma MEASUREMENTS: Serum measurements were made of 25 hydroxyvitamin D (25OHD), osteocalcin, and immunoreactive parathyroid hormone. Bone mineral density of the hip and spine was assessed by dual energy X-ray absorptiometry. PARTICIPANTS: A total of 77 Native American women aged 19 to 85 years. RESULTS: Serum 25 hydroxyvitamin D was related inversely to age (r = -0.32; P < .05) and was less than 15 ng/mL in 7% of the subjects. Serum osteocalcin was higher (P < .001) in postmenopausal than in premenopausal subjects. In postmenopausal subjects, serum osteocalcin was related to age (r = .59, P < .001). BMD was lower (P < .001) in postmenopausal than in premenopausal subjects. There was no evidence of bone loss before age 50 in either the femur or the spine. Age (r > or = -0.48, P < .001) and body mass index (BMI) (r > or = 0.41, P < .005) were independent determinants of both femoral and lumbar BMD. Serum 25OHD was a significant independent determinant of both lumbar (r = .26, P < .05) and femoral (r = .41, P < .01) BMD. Age, BMI, and serum 25OHD together accounted for 70% of the variance in BMD at these sites. The use of t scores indicated femoral bone density was higher (P < .05) in premenopausal Native American women, and lower (P < 0.05) in postmenopausal subjects, compared with white women. CONCLUSIONS: In Native American women, there is a reduction in bone density and a sustained increase in bone turnover postmenopausally. BMI and serum 25OHD are significant determinants of BMD. Peak BMD may be higher, and the postmenopausal rate of bone loss greater, than that in white women.

Adult↗
PubMed1998

Unilateral and segmental localised polycystic kidney disease.

Unilateral and segmental localised polycystic disease is a rare type of cystic disease of the kidney. It takes the form of a segmental cystic abnormality in one kidney morphologically identical to the autosomal dominant adult form of polycystic kidney disease. The clinical, radiological, and pathological appearances of a case are described. The differential diagnosis and a possible pathogenic mechanism are discussed.

Diagnosis, Differential↗
PubMed1998

Effect of recent alcohol intake on parathyroid hormone and mineral metabolism in men.

The mechanisms by which alcohol intake, particularly moderate alcohol intake, effects bone metabolism are poorly defined. We have examined the relationship between mineral metabolism and recent self-reported alcohol intake (SRAI) across a wide range of such intakes in a series of 104 men aged 32 to 78 years of age in an outpatient setting. A morning nonfasting urine, serum specimen and recent SRAI were obtained from each subject. SRAI was reported as between 0 and 45 oz/week. SRAI correlated positively with liver function tests, including serum bilirubin (r = 0.30, p = 0.002), alkaline phosphatase (r = 0.30, p = 0.004), and aspartate aminotransferase (SGOT) (r = 0.29, p = 0.006). SRAI correlated with serum calcium corrected for albumin (r = -0.39, p < 0.001), estradiol (r = 0.43, p < 0.001), and immunoreactive parathyroid hormone (iPTH) (r = -0.51, p < 0.001), as well as urinary calcium (per 100 mg of creatinine) (r = 0.55, p < 0.001). We have arbitrarily divided the participants into two groups on the basis of their reported alcohol intake. Individuals in the first group had intakes ranging from none to moderate intake (drank 8.4 oz or less of ethanol per week, equivalent to an average of two drinks daily or less). Those in the second group had moderate or heavier intake, with >8.4 oz of ethanol intake/week. Mean serum iPTH was significantly greater in those in the first group (none to moderate), compared with the second group (moderate or heavier) (56.0 +/- 3.4 and 39.9 +/- 2.0 pM/liter, respectively). Calcium corrected for serum albumin was significantly greater in individuals in the first, compared with the second, group (9.23 +/- 0.05 vs. 8.88 +/- 0.07 mg/dl, respectively). In addition, urinary calcium (corrected per 100 mg of creatinine) was significantly lower in the former, compared with the latter (3.1 +/- 0.4 vs. 8.4 +/- 1.1 mg/100 mg of creatinine, respectively). Similarly, urinary excretion of collagen crosslinks (corrected per 100 mg of creatinine) was significantly less in men in the second group, compared with the first group (316 +/- 38 vs. 530 +/- 78 nM/100 mg of creatinine, respectively). Not surprisingly, a series of correlations between iPTH and age, 250-hydroxyvitamin D, and testosterone were significant in individuals with none to moderate SRAI, but not moderate or heavier SRAI. Significant independent predictors of serum iPTH in the entire group of men were age (beta = 0.215, p = 0.025), SRAI (beta = -0.281, p = 0.003), 250-hydroxyvitamin D (beta = -0.309, p = 0.002), and testosterone (beta = -184, p = 0.048). We have concluded that, in free-living men, alcohol intake >8.4 oz/week was associated with decreased serum iPTH concentrations.

Adult↗
PubMed1997

Renin-1 is essential for normal renal juxtaglomerular cell granulation and macula densa morphology.

The secretion of renin from granules stored in renal juxtaglomerular cells plays a key role in blood pressure homeostasis. The synthesis and release of renin and the extent of granulation is regulated by several mechanisms including signaling from the macula densa, neuronal input, and blood pressure. Through the use of a gene-targeting vector containing homology arms generated using the polymerase chain reaction, we have inactivated the Ren-1(d) gene, one of two mouse genes encoding renin, and report that lack of renin-1(d) results in altered morphology of the macula densa of the kidney distal tubule and complete absence of juxtaglomerular cell granulation. Furthermore, Ren-1(d-/-) mice exhibit sexually dimorphic hypotension. The altered growth morphology of the macula densa in Ren-1(d)-null mice should provide a tool for the investigation of the JG cell-macula densa signaling. Furthermore, the current data indicate that expression of the Ren-1(d) gene is a prerequisite for the formation of storage granules, even though the related protein renin-2 is present in these mice, suggesting that renin-1(d) and renin-2 are secreted by distinct pathways in vivo.

Animals↗
PubMed1997

The Heidelberg classification of renal cell tumours.

This paper presents the conclusions of a workshop entitled 'Impact of Molecular Genetics on the Classification of Renal Cell Tumours', which was held in Heidelberg in October 1996. The focus on 'renal cell tumours' excludes any discussion of Wilms' tumour and its variants, or of tumours metastatic to the kidneys. The proposed classification subdivides renal cell tumours into benign and malignant parenchymal neoplasms and, where possible, limits each subcategory to the most commonly documented genetic abnormalities. Benign tumours are subclassified into metanephric adenoma and adenofibroma, papillary renal cell adenoma, and renal oncocytoma. Malignant tumours are subclassified into common or conventional renal cell carcinoma; papillary renal cell carcinoma; chromophobe renal cell carcinoma; collecting duct carcinoma, with medullary carcinoma of the kidney; and renal cell carcinoma, unclassified. This classification is based on current genetic knowledge, correlates with recognizable histological findings, and is applicable to routine diagnostic practice.

Humans↗
PubMed1997

Molecular genetic analyses of parapoxviruses pathogenic for humans.

The current members of the genus parapoxvirus are orf virus (ORFV), bovine papular stomatitis virus (BPSV), pseudocowpoxvirus (PCPV) and parapoxvirus of red deer in New Zealand (PVNZ). BPSV and PCPV are maintained in cattle while ORFV is maintained in sheep and goats, but all three are zoonoses. Only the recently reported PVNZ has yet to be recorded as infecting humans. Tentative members of the genus are camel contagious ecthyma virus, chamois contagious ecthyma virus and sealpoxvirus. The separation of the parapoxviruses into 4 distinct groups has been based on natural host range, pathology and, more recently, on restriction endonuclease and DNA/DNA hybridisation analyses. The latter studies have shown that the parapoxviruses share extensive homology between central regions of their genomes, but much lower levels of relatedness within the genome termini. The high G + C content of parapoxvirus DNA is in contrast to most other poxviruses and suggests that a significant genetic divergence from other genera of this family has occurred. DNA sequencing of portions of the genome of ORFV, the type species of the genus, has allowed a detailed comparison with the fully sequenced genome of the orthopoxvirus, vaccinia virus (VACV). These studies have provided a genetic map of ORFV and revealed a central core of 88 kbp within which the genomic content was strikingly similar to that of VACV. This conservation is not maintained in the genome termini where insertions, deletions and translocations have occurred. The characterisation of specific ORFV genes may lead to the construction of attenuated vaccine strains in which genes such as those with the potential to interfere with the immune response of the host have been deleted. The current ORFV vaccines are living unattenuated virus and vaccination lesions produce virus which contaminates the environment in a manner similar to natural infection. The virus in scab material is relatively resistant to inactivation and this virus both perpetuates the disease in sheep and provides the most likely source of human infections. A vaccine which immunises animals without perpetuating the disease could be the best way of reducing the incidence of ORFV infection of humans. It is likely that protection against infection by ORFV is cell mediated and will require the endogenous production of relevant antigens. We have recently constructed a series of VACV recombinants each of which contains a large multigene fragment of ORFV DNA. Together the recombinants represent essentially all of the ORFV genome in an overlapping manner. Vaccination of sheep with the recombinant library provided protection against challenge with virulent ORFV. Further studies with this library may enable dominant protective antigens of ORFV to be identified and lead to their incorporation into a subunit vaccine.

Animals↗
PubMed1997

Genetics of renal tumours.

The two main renal tumours, Wilms' tumour and renal cell carcinoma, are associated with distinct molecular genetic abnormalities. The genes involved behave as Knudson oncosuppressor genes. Further dissection of the molecular biology pathways involving WT1 and VHL genes is providing fascinating insight into the biology of these genes, the development and cell biology of the kidney and its tumours.

Beckwith-Wiedemann Syndrome↗
PubMed1997

The renal pathology of mushroom poisoning.

We present the histology and electromicroscopy of renal failure caused by ingestion of the mushroom species Cortinarius speciosissimus. Light microscopy revealed acute tubular necrosis, multinucleated tubular epithelial cells and concentric medial muscular hyperplasia of arteries. Electronmicroscopy showed the displaced and abnormal architecture of actin filaments at the periphery of the cytoplasm in renal tubular epithelial cells.

Adult↗
PubMed1997

The effect of the anaesthetic, Propofol, on in-vitro oocyte maturation, fertilization and cleavage in mice.

Propofol is a common anaesthetic agent used for oocyte retrieval procedures during in-vitro fertilization (IVF). The effect of Propofol in vitro on mouse oocyte maturation, fertilization and embryo cleavage was studied. In this study, 551 cumulus-free and 222 cumulus-enclosed oocytes from mice stimulated with pregnant mare's serum gonadotrophin (PMSG) were incubated for 30 min in medium containing 0, 100, 1000 or 10,000 ng/ml of Propofol prior to in-vitro maturation. Also, 325 cumulus-enclosed oocytes from mice stimulated to ovulate with PMSG/human chorionic gonadotrophin (HCG) were incubated for 30 min in similar concentrations of Propofol prior to IVF. Maturation, fertilization and cleavage rates were compared. A significant decrease in the in-vitro maturation rate was observed only when the cumulus-free and cumulus-enclosed oocytes were exposed to 10,000 ng/ml Propofol (P < 0.0074 and P < 0.0001 respectively). Fertilization and embryo cleavage rates were not significantly different compared with the controls. These findings give some reassurance with respect to human IVF. However, further studies on the potential effects of Propofol on implantation and pregnancy outcome following IVF are needed.

Anesthetics, Intravenous↗
PubMed1997

Localization of fibrillin-1 in human endometrium and decidua during the menstrual cycle and pregnancy.

We have examined the existence and distribution of fibrillin-1 within the endometrium and decidua to ascertain the effect of decidualization upon its synthesis, and its relationship to other extracellular matrix proteins. Formalin-fixed, paraffin-embedded tissues were stained using monoclonal antibodies to collagen IV, elastin, fibrillin-1 and laminin, by immunocytochemistry. Fibrillin-1 was present throughout the menstrual cycle and appeared to be cell-associated. Similar staining for fibrillin-1 was detected within the Fallopian tube of ectopic pregnancy material. In first trimester, second trimester and term decidua, staining for fibrillin-1 was more intense than that during the menstrual cycle and was detected as a thick layer encapsulating decidual cells, but also in fibrillar form inter-connecting these cells. In comparison with the association of collagen IV and laminin with all basal laminae, fibrillin-1 was absent from the vascular and glandular elements of pregnancy endometrium. Elastin was absent in all tissues examined. Hence, fibrillin-1 exists within the uterus in association with basal lamina components rather than with elastin-containing fibrils, where its presence in the endometrium and decidua could be of functional significance.

Antibodies, Monoclonal↗
PubMed1997

Distribution of integrins and the extracellular matrix proteins in the baboon endometrium during the menstrual cycle and early pregnancy.

Integrins are heterodimeric glycoproteins that have been found to undergo dynamic temporal and spatial changes in distribution in the endometrium during the menstrual cycle in women. Likewise the extracellular matrix (ECM) ligands for these receptors are likely to play a role in the establishment of a receptive endometrium. To develop primate models to study the role of these molecules in the cascade of molecular events leading to implantation, integrin expression and associated changes in ECM were investigated during the menstrual cycle and in early pregnancy in the baboon. Antibodies specific for the integrins (alpha(1-6) and alpha(v); beta1, beta3, and beta4) and ECM (laminin, collagen IV, fibronectin) were utilized. In addition, cytokeratin and alpha-smooth muscle actin were used as epithelial, stromal, and smooth muscle cell markers, respectively. Endometrium was obtained in duplicate or triplicate during the menstrual cycle and early pregnancy. Changes observed during the natural menstrual cycle were confirmed using ovariectomized, steroid-treated animals. Constitutively expressed integrins on the endometrial epithelium included the collagen/laminin receptors: alpha2, alpha3, alpha6, and beta4. The pattern of expression correlated well with the distribution of ECM in this tissue. Collagen IV was confined to the basement membrane of glandular epithelium and blood vessels. Laminin immunostaining was found in the basement membrane, mostly in the stroma of the basal region, in the glandular endometrium and vasculature. Fibronectin was present throughout the stroma but not in the basement membrane. The collagen receptor alpha1 beta1 and fibronectin receptor alpha4 beta1 appeared in the glandular epithelium in the luteal phase. As in the human, alpha1 and alpha4 disappeared from the glandular epithelium with the establishment of pregnancy. In contrast, the alpha4 beta3 vitronectin receptor appeared in the glandular epithelium only in pregnancy or following long-term steroid treatment with estrogen and progesterone but not during the time of uterine receptivity associated with the initial period of embryo attachment. Osteopontin, an ECM ligand for alpha(v) beta3, was coexpressed with this integrin in invading cytotrophoblasts, glandular epithelium, and decidualizing stromal cells. Decidualization in the baboon was associated with changes in integrin expression similar to those found in humans: there was an increase in alpha1, alpha3, alpha6, beta1, and alpha(v) beta3 in the decidualized stromal cells. Laminin and collagen IV expression also increased at the implantation site and throughout the endometrium. In contrast, fibronectin expression was most evident at the implantation site and corresponded to alpha5 expression on the invading cytotrophoblasts. In summary, marked similarities were found in the expression of ECM and the integrin receptors between the baboon and the human endometrium throughout the menstrual cycle and in pregnancy. Cycle-specific integrins, alpha1, and alpha4, were present on epithelial cells during the secretory phase. Delayed expression of alpha(v) beta3 in baboon endometrial glands correlated closely with the time of enhanced glandular secretory activity in this primate. The baboon appears to be an excellent model for the investigation of the role of integrins and ECM leading to successful implantation.

Animals↗
PubMed1997

Enhanced major histocompatibility complex (MHC) class II antigen expression in lupus nephritis.

Thirty-eight cases of lupus nephritis, all satisfying the American Rheumatism Association criteria for diagnosis of systemic lupus erythematosus (SLE), with renal involvement and biopsy were immunohistochemically studied for the expression of HLA-DR (DAKO: HLA-DR/alpha, TAL.1B5), one of the three known families belonging to the class II major histocompatibility complex (MHC), using a standard streptavidin-biotin-peroxidase method. 20 nephrectomies performed for renal trauma and tumours constituted the normal controls. Of the lupus nephritis cases, 34 were females and 4 males. Ethnically, 20 were Chinese, 13 Malay, 4 Indian and 1 of indigenous origin. Their ages ranged from 16 to 59 years (mean of 31 years). Histologically, 23 expressed World Health Organisation (WHO) class IV (diffuse proliferative), 10 WHO class V (diffuse membranous), 4 WHO class II (pure mesangiopathy) and 1 WHO class III (segmental and focal proliferative) nephritis. Activity scores ranged between 5 to 19 (mean = 8.6) and chronicity scored between 2 to 7 (mean = 3.2) on a standard scoring system. Similar to other studies, HLA-DR was expressed in the glomerular capillaries and peritubular capillaries of all and mesangium, tubules (proximal, distal and collecting), veins and arterioles of some normal controls. Interestingly, HLA-DR expression was noted in the arteries of 25% of the normal controls, a finding hitherto not reported. The frequency of lupus nephritis cases expressing HLA-DR in the various anatomical components did not differ significantly from the normal controls except that HLA-DR expression in arteries and arterioles was seen at a significantly increased frequency (p < 0.01) in lupus nephritis. This increased expression did not correlate with the WHO class, activity or chronicity scores. It therefore appears that MHC class II shows increased expression in the arterial system of lupus nephritis kidneys. The significance of this is unclear but could be related to heightened (gamma-interferon activation which may be a de novo phenomenon or result of T cell proliferation and activation in SLE.

Adolescent↗
PubMed1996

Psychosexual development of women with congenital adrenal hyperplasia.

Women with congenital adrenal hyperplasia (CAH) (N = 31) and their unaffected sisters or female cousins (N = 15) participated in a study of psychosexual development. All participants were > or = 18 years of age (mean age, 25 years; range, 18-40). Comparisons were also made between the CAH women with the salt-wasting (SW) form of the disorder and those with simple virilization (SV). A psychosexual assessment protocol examined six variables: (1) sex assignment at birth (probands only); (2) recalled sex-typed behavior during childhood; (3) gender identity and gender role identification in adulthood; (4) relationship status; (5) sexual orientation in fantasy; and (6) sexual orientation in behavior. Salt-wasting status and sex assignment at birth were also ascertained for the CAH women who either refused to participate in the study (N = 10) or could not be traced (N = 13). Compared to the controls, the women with CAH recalled more cross-gender role behavior and less comfort with their sense of "femininity" during childhood. The two groups did not differ in degree of gender dysphoria in adulthood, although the probands showed more cross-gender role identification. Three of the nonparticipant probands were living, as adults, in the male social role (2 reared from birth as boys and 1 who changed from the female to the male social role during adolescence). The CAH women and the controls did not differ in relationship status (married/cohabiting vs. single). The CAH women had lower rates of exclusive heterosexual fantasy and fewer sexual experiences with men than the controls; however, the CAH women did not have more sexual experiences with women than the controls. Comparisons between the SW and SV revealed several differences: the SW were less likely to be assigned to the female sex at birth, recalled more cross-gender role behavior during childhood, were less likely to be married or cohabiting, and had lower rates of sexual experiences with men. The results were discussed in relation to the effects of prenatal androgens on psychosexual differentiation.

Adrenal Hyperplasia, Congenital↗
PubMed1996

Expression of the von Hippel-Lindau disease tumour suppressor gene during human embryogenesis.

The von Hippel-Lindau (VHL) disease product is thought to down-regulate transcription by antagonizing elongin-enhanced transcriptional elongation. Germline VHL gene mutations predispose to the development of retinal, cerebellar and spinal haemangioblastomas, renal cell carcinoma and phaeochromocytoma. In addition, somatic Inactivation of the VHL gene is frequent in sporadic renal cell carcinoma and haemangioblastoma. Regulation of transcript elongation is an important control mechanism for gene expression and the VHL gene might modify the expression of proto-oncogenes and growth suppressor genes during embryogenesis. We therefore investigated the expression of VHL mRNA during human embryogenesis by in situ hybridization studies at 4, 6 and 10 weeks post conception. Although VHL mRNA was expressed in all three germ layers, strong expression was noted in the central nervous system, kidneys, testis and lung. Within the kidney, VHL mRNA was differentially expressed within renal tubules suggesting that the VHL gene product may have a specific role in kidney development. Two alternatively spliced VHL mRNAs characterized by inclusion (isoform I) or exclusion (isoform II) of exon 2 are transcribed in adult tissues. To investigate if the two isoforms are differentially expressed during embryogenesis, VHL mRNA was reverse transcribed from 13 fetal tissues (8-10 weeks gestation). The quantitative distribution of VHL mRNA within fetal tissues reflected that seen by in situ hybridization and the ratio of the two VHL isoforms was similar between tissues. Although the genes regulated by the VHL gene product have not yet been identified, our findings are compatible with the hypothesis that VHL-mediated control of transcriptional elongation may have a role in normal human development.

Adult↗
PubMed1996

Immunohistochemical localization of extracellular matrix proteins in luteal phase endometrium of fertile and infertile patients.

The lack of expression of certain components involved in cell adhesion and migration is believed to contribute to endometrial dysfunction and implantation failure. The purpose of this study was to investigate whether luteal phase endometrium in women with unexplained infertility differs, with respect to specific extracellular matrix (ECM) proteins, from endometrium of normal fertile women. A panel of monoclonal antibodies to collagen type IV, fibronectin and laminin was used to characterize the localization of ECM components in the different endometrial compartments. Precisely timed endometrial biopsies obtained at 4, 7, 10 and 13 days following the luteinizing hormone surge were obtained from 22 normal fertile women (group 1) and 24 women suffering from unexplained infertility (group 2). Paraffin-embedded sections were labelled using the streptavidin-biotin alkaline phosphatase technique. In group 1, collagen type IV, fibronectin and laminin were absent from the luminal epithelium but present in stromal cells and the basement membrane of glands and blood vessels. In group 2, these components were absent from all endometrial regions using equivalent titres of antibody to those used in group 1. This suggests that the endometrium of women with unexplained infertility demonstrates defects in the distribution of certain ECM glycoproteins. A possible consequence of this defect may be implantation failure.

Adult↗
PubMed1996

Scintigraphic quantification of aspiration reduction with the Passy-Muir valve.

The Passy-Muir "speaking" tracheostomy valve has been noted to aid in swallowing, based on videofluoroscopy to assess aspiration. In this study scintigraphy was used to quantify the amount of material aspirated. Eleven patients were studied who currently had a tracheostomy in place and were either known to aspirate or were suspected of aspirating. Most were post-treatment head and neck cancer patients who were tumor free at the time of testing. Swallowing was evaluated using videofluoroscopy and scintigraphy. Videofluoroscopy was performed to assess anatomy and determine whether aspiration had occurred. Scintigraphic testing was then performed when the patient had the one-way valve on, and again with it off and tracheostomy open. Following a swallow, the amount (%) of aspirate with the valve in place was found to be significantly less than with the tracheostomy open. A one-way valve can be helpful in reducing aspiration in patients who are at risk for aspiration and who require that their tracheostomy be open.

Humans↗